Alkyl-2,3,3-triiodoallyl ethers and process for their preparation and a composition containing the same

ABSTRACT

Novel alkyl 2,3,3-triiodoallyl ethers useful as disinfectants are provided by an addition reaction of alkyl-3-iodo-2-propinyl ethers with iodine. The starting alkyl-3-iodo-2-propinyl ethers can be prepared by a new process comrising an alkylation of propargyl alcohol with an alkyl sulfate or alkyl sulfonate in the presence of an alkali, followed by monoiodization of the resulting alkyl-2-propinyl ether. This invention also provides a composition comprising alkyl 2,3,3-triiodoalkyl ethers useful as a poultry feed additive having growth increasing effects and for treating swine scours.

United States Patent Sekizawa et al.

[111 3,859,362 Jan. 7, 1975 [75] Inventors: Yasuharu Sekizawa;'Shige0 Seki;

Bunzo Nomiya, all of Tokyo; Takemi Koeda, Yokohama; Fumio Kai, Fujisawa; Naotoshi Akai,

' Tokyo; Yasushi Yusa; Fuguaki Fukuyasu, both of Yokohama, all of Japan [73] Assignee: Meiji Seika Kaisha Ltd., Tokyo,

Japan [22] Filed: Dec. 29, 1972 [2]] Appl. NO.:'319,127

[52] US. Cl. 260/614 R, 99/2 G, 99/2 AB, 204/158, 424/339, 424/342 [51'] Int. Cl...... C07c 43/00 [58] Field of Search 260/614 R [56] References Cited UNITED STATES PATENTS 2,079,758 5/1937 Berchet 260/614R 2,462,830 3/1949 Cass ..l ..260/614A OTHER PUBLICATIONS 'Freidlina et al., Chem. Abst., 50, 4767H, 1956.

Balog et al.,'Chem. Abst., 54, l725 5a, 1960. Nikishin et aL, Chem. AbsL, 66, 85224m, 1967.

Primary Examiner'H0ward T. Mars Attorney, Agent, or Firm-Sughrue, Rothwell, Mion, Zinn & Macpeak [57] ABSTRACT presence of an alkali, followed by monoiodization of the resulting alkyl-2-propinyl ether. This invention also provides a composition comprisingilkyl 2,3 ,3- triiodoalkyl ethers useful as a poultry feed additive having growth increasing effects and fortreating swine SCOLll'S.

5 Claims, No Drawings LQJQ -TRIIOD LL E HERS. A PROCESS FOR THEIR PREPARATION AND A J COMPOSITION CONTAINING THE SAME I BACKGROUND OF THE INVENTION Field of the Invention The present invention relates .to alkyl 2,3,3 triiodoalkyl ethers and processes for preparing the same as well as compositions containing alkyl 2,3,3-

triiodoalkyl ethers.

Summary of the Invention The inventors have discovered that novel alkyl 2,3,3- triiodo ethers which are useful as excellent feed additives for growing poultry or as agents for treating swine scours. More especially, this invention relates to alkyl 2,3,3-triiodoallyl ethers of the following formula:'

. dition reaction of alkyl-3-iodo-2-propinyl ethers of the following formula:

.wherein R. isthe same as defined with respect to for mula (I), with iodine. This process has not been known previously, and the reaction involved is one of the important advantages of the present invention. The addition reaction alone isinduced selectively by using the alkyl-3-iodo-2-propinyl ethers of formula (II) as starting materials, and therefore, the final products (I) of high purity can be formed in high yields. The purification of the products can be performed easily on an industrial scale, and moreover, the starting materials are available at low cost.

The present invention further provides a process for preparing alkyl-3-iodo-2-p'ropinyl ethers of formula (II) by reacting propargyl alcohol with an alkyl sulfate or alkyl sulfonate in the presenceof an alkali to form an alkyl-Z-propinyl ether of the following formula:

described. For example, methyl-i-iodd-Z-propinyl I ethe'r.(R=methyl in formula (II)), one of the starting compounds of formula (II), can .be prepared by the known method disclosed in R. Lespicau, Ann. Chim. (Paris), Vol. II, page 269 (1,897), but it is not commercially advantageous.

Accordingly, in another aspect of this invention, there is provided a process for preparing alkyl- 3-iodo- 2-propinyl ethers of formula (II), which comprises reacting propargyl alcohol with an alkyl sulfate or alkyl sulfonate in the presence of an alkali to form an alkyl- 2-propinyl ether of the following formula:

' wherein R is the same as defined with respect to for wherein R is the same as defined in formula (I), and

p then monoiodizing the alkyI-Z-propinyl ether.

DETAILED DESCRIPTION OF THE INVENTION Some of the compounds of formula (II) are known compounds, but most of them are novel compounds which can be prepared easily by a new method to be mula (I), and then monoiodizing the alkyl-2-propinyl ether.

Unlike the conventional method, this new process does not go through a propargyl halogenide or. dihalopropyl-methyl ether as an intermediate, but yields the alkyl-2-propinyl ether by alkylation of propargyl alcohol, Specifically, the alkyl-Z-propinyl ether is obtained in a very high yield by reacting propargyl alcohol in the form of an aqueoussolution or in the absence of solvent with an alkyl sulfate or alkyl sulfonate in the presence of an alkali hydroxide.

The compound of formula (III) can also be obtained by reacting a propargyl halogenide or a propargyl ester of sulfonic acid with a corresponding alcohol in the presence of alkali, but this method is drastically disad vantageous as compared with the process of this invention. i l

The aIkyI-Z-propinyl ether of formula (III) obtained can be purified by distillation prior to iodization or may be used without further purification by'distillation. If the inorganic salt formed during the reaction is precipitated, an appropriate organic solvent or water may be added to the reaction mixture prior to iodization in an amount sufficient to dissolve the salt. A solution of an alkali metal hydroxide or alkaline earth metal hydroxide in water or a lower alcohol, e.g., lower alkanol such as methanol, ethanol, propanol and iso-propanol is added to the alkyl-Z-propinylether in an amount of 1 to 2 moles of the hydroxide per one mole of the ether, and while the mixture is being stirred 'at near room temperature, an aqueous solution of l 1.2 moles of iodine or an aqueous mixture of iodine withpotassium iodide is usually added in an'amount of from 1 to 1.2 molesof iodine per 1 mole of the ether. Iodine and potassium iodide may be used in'an equim'olar amount. This induces the monoiodization of the alkyl-3-iodo-2- propinyl ether of the formula (II) in a high yield.

Alternatively, the compound of formula (II) may be obtained by a process which involves treating the compound of formula (III) with a copper complex salt, a copper salt or cuprous hydroxide to convert it to its cupric acetylide and monoiodizing it with iodine to form the-compound of formula (II).

In these processes, the same results can be achieved by using an iodonium salt solution comprising iodine and potassium iodide instead of iodineQGenerally, the

solventmay be water'or a lower alcohol.

According to the above methods, the selective monoiodine substitution of the acetylenic hydrogen of the compound of formula (III) is carried out in a high yield. lodine is very much liable to add to such an acetylenic bond, and intrinsically the addition reaction predominates to form the corresponding alkyl-2,3-iodo allyl-ether. However, as a result of activating the terminal carbon of the acetylenic bond by a basic catalyst such as an alkalihydroxide or copper ions or copper complex ions. 'in the abovementioned processes, the first-stage monoiodine substitution reaction takes place selectively, whereas the formation of an alkyl-2,3-iodoallyl ether, which is the outcome of the undesirable side-reaction, can be reduced.

The monoiodine substitution reaction described above can also be performed by reacting the compound of formula (11) with iodine in liquid ammonia; or by using an organic amine such as morpholine or triethyl amine as the basic catalyst.

The novel alkyl-2,'3,3 -triiodoallyl ether of formula (I) isprepared by adding a solution of iodine or an iodonium salt to the compound of formula (II) which is either purified, for example, by distillation underreduced pressure, or in the crude form as asolution in a suitable solvent, and stirring the mixture. This process can be carried-out at any temperature, but temperatures in the range of from room temperature to a boiling point of the solvent used are preferred. The iodine oran iodinium salt is generally used in an amount of from an, equimolar amount to a molar excess amount with respect to the compound of formula (II).

The solvent suitable for use in this reaction is a compound which does not react with iodine. Examples of the solvent are chloroform, dichlorome'thane, carbon tetrachloride, dioxane, lower alcohols, acetic acid or water.

The iodine addition reaction is promoted even at low temperatures (below room temperature) by exposing the'reaction mixture to the irradiation of light during the reaction, and this can lead to the shortening of the time required until the completion of the reaction. The

light irradiation also minimizes a decomposition reac-- tion that may occur during heating, and frequently, the product is obtained in a very good yield The use of an excess of iodine (usually, about 1.1 to

duce 2,3,3-triiodoallyl alcohol in a single step. Theresulting triiodoallyl alcohol is generally sparingly soluble in the above described aqueous solvent, but is easily soluble in dipolar aprotic solvents and can be alkylated with an appropriate alkylating agent in the dipolar aprotic solvents such as dimethylformamide, dimethylsulfoxide and the like to obtain thedesired product. Also, the above triiodoallyl alcohols may be converted first into their reactive derivatives, i.e., 2,3,3- triiodoallyl halogenides or pseudo halogenides such as p-toluenesulfonateor methanesulfonate in the presence of an alkali, and the resulting halogenides or pseudo halogenides can then be alkylated by treating with an alkali metal alkoxide'or subjecting to alcoholysis in the presence of an alkali hydroxide to obtain the desired products. p

The composition of this invention comprises an alkyl 2,3,3-triiodo-ally methyl ether as an active ingredient, which is useful as a feed additive for growing poultry orv as an agent for treating the swine scours.

1.5 times) can also shorten the time required until the After the reaction, excess iodine is removed by adding an aqueous solution of sodium thiosulfate, shaking the mixture and removing the aqueous layer. The final product can be obtained 'by washing the solvent layer with water, concentrating and crystallizing it, and fi- The 2,3,3-triiodo-allyl methyl ether which is a typical compound of this invention has a melting point of 43-.5

Table l Antimicrobial spectrum of 2,3,3-'

triiodo-allyl methyl ether' Bacteria Minimum inhibition concentration (meg/ml) Staphylococcus aureus 209-p 6.25 Streptococcus haemolyticus cook 12.5 Diplococcus pneumoniae Type 1 10 1 Bacillus subtilis H21 219 10 1 Salmonella typhi-O-901-W 3.12. Escherichia coli Communis '10 1 0-16 6.25 0-20 0.78 0-78 3.12 0-83 12.5 0-135 3.12 0-139 12.5. 0-142 6.25 Mycobacterium tuberculosis H37RV 10 1 El-tor vibrio 3.12 Tricophyton asteroides I 1.56. Aspergillus fumigatus Saitq 3.12 Candida albicans Totuka 3.12 Cryptococcus neot'ormans 301 0.78

This compound has low toxicity against poultry and I swine as demonstrated by LD values on mice which nally recrystalliz ing it from a suitable solvent. When the product is a liquid, the remaining oily material is purified bydistillationunder reduced pressure or by alumina chromatography to isolate it as a pure substance.

wherein R is as defined above, can be prepared by an alternative procedure. Propargyl alcohol is reacted with iodine in the presenceof an alkali hydroxide in an aqueous solvent which is inert to iodine, for example,

are shown in Table 2.

Table 2 ToxicitytLD) against mice more than 1000 mg/Kg 50"-l00 mg/Kg Oral administration lntraperitonesl administration As is well known, LD or the median lethal dose, is the 7 test material is.

. The 2,3,3-triiodo-allylmethyl ether is prepared, for example, by an addition reaction of 3-iodo-2-propinyl- I methyl ether'with iodine;

It has now been found that 2,3,3-triiodo-allyl-methyl ether is a feed additive having excellent growth effects on poultry which does not overlap pharmaceuticals for treating human diseases, is hardly absorbed by the digestive tract of poultry, is free from residue build-up and does not have cross resistance.

It has been the practice in the poultry production in-' dustry to raise poultry with feeds having incorporated therein small amounts of various antibiotics for the purpose of preventing diseases and increasing poultry growth. However, many of the antibiotics effectively used for these purposes are primarily intended for treating human diseases. It has been pointed out that prolonged use of such antibiotics in poultry feeds contributes to the evolution of resistant strains of bacteria which when evacuated from the poultry together with excrement, may cause environmental pollution, which in turn may result in problems in treating human diseases. Even those antibiotics not applied to humans, if they have a cross resistance effect, are undesirable for the same reason. It has also been pointed out that when such an antibiotic remains in the edible parts of poultry, it can possibly cause allergies in the human body. Steroid hormones, on the other hand, were once added to poultry feeds for the purpose of growth stimulation, but were prohibited when it was found that their residues built up and exerted adverse effects on the human body. l

' Feed additives for growth purposes desirably have effects on clusters of bacteria normally present in the intestines when they pass through the digestive tract with the feeds. It is clearlyseen from Table 1 that 2,3,3-triiodo-ally-methyl ether is effective against such I bacteria.

It is also desirable that growth effects are obtained by adding the additive in a small amount to the poultry feeds, but that even large amounts of the additive do not exert adverse effects. The safety of the feed additive according to the present invention is clearly seen from Table 2. An LD value of more than 1,000 mg per kilogram of the body weight of a mouse in oral administration shows that 2,3,3-triiodo-allyl-methyl ether powder ordiluted l0-fo1d with lactose. It is used in an amount of about mg or more, per kilogram of the body weight of the swine in one dosage, and may be increased according to the case. Usually, it is administered twice on the first day, and thereafter, once a day.

for 3 to 4 days. By this method of treatment, the disease is generally cured in about 5 days.

is an excellent poultry feed additive. On the other hand,

an LD of 50-100 mg per kilogram of the body weight of a mouse in intraperitoneal administration'means relatively low toxicity. It is due to the difficulty of absorption of 2,3,S-triiodo-allyl-methyl ether from the intestiinvention, there is provided an. agent for treating swine scours comprising utilizing 2,3,3-triiodoallyl-methyl ether as an active ingredient, which compound does not overlappharmaceuticals for treating human diseases, does not have cross resistance, is hardly absorbed by the digestive tract of swine and which does not cause a buildup of residue in the system of the swine.

It is well known that serious scours occurs in the breeding of young swine which causes great damage to The following Examples specifically illustrate the present invention.

EXAMPLE 1 Preparation of Methyl-2,3,3-Triiodoallylether 16 Grams of 3-iodo-2-propinyl-methyl ether was dis solved in ml. of chloroform, and 25.4 g of iodine powder was added. The mixture was heated under reflux for 3 hours at a bath temperature of 70C., and

then allowed to stand overnight at room temperature.

It was further heated at 70C and shaken with the gradual addition of a 1N aqueous solution of sodium thiosulfate until the color of the iodine disappeared. The aqueous layer which was formed was removed. The chloroform layer was washed with water, and by evaporating off the solvent at reduced pressure, about 30 g of crude crystals were obtained. The crude crystals were recrystallized from methanol toprovide 29.5 g (yield 79 percent) of almost colorless pillarto platelike crystals having a melting point of 435 to 44.5C.

Elemental analysis values C l-1.01:, (450i Calculated: c io.o7 14 1.12 Found c 9.62 H l.31

NMR(CC1.). r 6(ppm); 3.32 (singlet. 3H, CH,,O-),

4.04 (singlet, 2H, CH,0--)

(Note: The 6 values of NMR are those obtained using letramethylsilane as'an internal reference.)

' EXAMPLE 2 Preparation of ethyl-2,3,3-triiodoallylether 16 Grams of ethyI-B-iodo-Zpropinyl ether (b.p. 50-5 2C./4 mmHg) was dissolved in ml. of chloroform,and 20 g of iodine was added. With stirring, white perature below 10C. by ice cooling. When the color of the iodine almost disappeared, a 1N aqueous solution of sodium thiosulfate was added to the reaction mixture and the mixture was stirred to remove unreacted iodine. The chloroform layer was washed with water and dried with anhydrous sodium sulfate. The solvent was then evaporated off to give 32 g of an oily material which was found to be almost pure ethyl-2,3,3- triiodoallyl ether (R=eth yl in formula '(l)). Distillation of this oily material at reduced pressure provided a liqu id having a boiling-point of 108 to 110C. at 0.27 mml-lg.

N'MR (coca). 6 (ppm), 1.36 (triplet, .l=7 cps, 3H,

' 4.19(singlet,2H, OCH).

I I EXAMPLE 3 Preparation of isopropyl-2,3,3-triiodoallyl ether 2.8 Grams of isopropyl-3-iodo-2-propinyl ether (b.p.

' -63-65.C/6mmHg) was dissolved in 30 ml. of chloroform and 3.2 g of iodine was added thereto. The mixture was then subjected to the same reaction and posttreatmentprocedures as in Example 2. Finally, chloroform was evaporated off from the chloroform extract to provide 4.65 .g (yield 775 percent) of crystals. Recrystallization of the crystals from methanol yielded 3.25 g of colorless crystals having 'a melting point of 43.5 to 44C. l

Elemental analysis values. C,H,Ol, (477.8)

' Calculated: C 15.07 H 1390 Found: C 15.07 H 1.82

EXAMPLE 4 Preparation of ,n-propyl-2,3,3'-triiodoallyl ether 8.4 Grams of n-propyl-3-iodo-2 propinyl ether (b.p.

691-70C/5.2 mmHg) was dissolved in 50 ml. orslild d form' and 9.5 g'of'iodine. The mixture was subjected to the same reaction and post-treatment procedures as in Example 2. Finally, chloroform was evaporated off from the chloroform extract to give 17.3 g of an oily material. This material was dissolved in methanol to crystallize it. There was obtained 12.8 g of light yellow crystals having a melting point of 3 3.5 to 34C.

Elemental analysis values c,li',ol, 447.8)

Calculated: C 15.07

'H 1.90 I I Found: C 15.05 H 1.89 i

EXAMPLE 5 Preparation of 3-iodo-propinyl methyl ether 3o mml-lg, 'yield 84.5 percent), isopropyl-3-iodo-2- boiling point of 58 to 65C. This product was identified as methyl propargyl ether (purity about 78 percent, yield 96 percent) containing a'small amount of methanol by means of gas-chromatography and NMR spectrum.

NMR CDCl, a pm 4.07 (doublet, J=2 cps, 2H,

CH O), 3.36 (singlet, 3H, O,'-CH 2.48 (triplet, J=2 cps, 1H, HC=C). Further, the NMR spectrum showed a signal at 3.27 ppm based on the methyl group proton of methanol.

' 7 Grams of the methyl-propargyl ether (containing about 22 percent of methanol) obtained above was admixed with a solution of 1 1.2 g of potassium hydroxide in 20 ml. of water. While the mixture was being thoroughly stirred at room temperature, 25.4 g of iodine was added in several portions. The mixture was stirred at room temperature for about 1 hour. The product was 44.8 Grams of propargyl alcohol and 93:4 of 96 percent potassium hydroxide were dissolved in 80 ml. of water. While the aqueous solution obtained was being'maintained at about 15C with stirring, 100.8 g

of dimethyl sulfate was added dropwise thereto over the course of about 1- hour, and then the mixture was further heatedat 60C. for lfhour. A distillation tube was attached to the reactor used. The mixture was heated at about 60C. with stirring, and the distillate was collected. Finally, the bath temperature was raised to about 80C., and all the liquid. that distilled-out was collected. The yield was 61 g, and the distillate had a v extracted with 50 ml. of chloroform. The chloroform propinyl ether (b.p. es ss-"c e mmHg, yield 51.0 sicent), and n-propyl-3-iodo-2-propinyl ether (b.p.

69-70C/5.2 mmI-lg, yield 74.5 Percent). (The above' yield values are on a molar basis based on propargyl alcohol).

'EIXAMPLEG Preparation of methyl-2,3,3-triiodoallyl ether 1.15 g of '2,3,3 -triiodoallyliodide (m.p. 80-81C,'

prepared by the addition reaction of 1,3-diiodopropyne and iodine) was dissolved in 35ml of methanol, and to the mixture was then added 2 ml of 1.05N Kori/ma thanol followed by allowing the mixture tostand at a temperature of 30C for 24 hours.- The mixture was then concentrated under reduced pressure at a temperature below 40C, andml of water was added thereto followed by standing overnight at 0C. An oil first formed and gradually crystallised to give 890 mg of crude crystals. Recrystallization from methanol yielded 496 mg (52 percent yield) of a pale yellow crystalline product having a melting point of 42-43.5C.

EXAMPLE '7 v Preparation of methyl 2,3,- 3-triiodo'allyl ether 8.72 g of 2,3,3-triiodoallyl alcohol (m.p. 152-15'3C, prepared by reacting propargyl alcohol'with iodine in the presence of an alkali) was dissolved in 20ml of'dimethylformamide, and 3.8 g of di'rnethyl sulfate and so- .lution of 1.3 g of sodium hydroxide in 5 mlof water were successively added dropwise with stirring over 1' hour, while maintaining the temperature of the reaction mixture ,in the range of to C during the ad'- dition by external cooling with water. After completion of the addition, the mixture was stirred at a temperature of C for minutes, and ml of ice-water was added to precipitate a crystalline product. The thus obrained crystals were separated by filtration, and washed first with water and then with a small amount of cold methanol to give 7.5 g (83.3 percent yield) of the product having a ,melting point of 42-43C.

EXAMPLE 8 Preparation of methyl 2,3,3-triiodoallyl ether I 4.36 g of 2,3,3-triiodoallyl alcohol was dissolved in 10 ml of dimethylformamide, and 4.26 g of methyl iodide and a solution of 0.8 g of of sodium hydroxide in 3 ml of water were successively added dropwise with stirring and ice-cooling over a period of about 30 minutes. After completion of the addition, the mixture was stirred for 5 hours at a temperature of 25C and 50 ml of ice-water was added thereto to precipitate a crystalline product. The thus obtained crystals were separated by filtration, and washed first with water and then with a small amount of cold methanol to give 3.9 g (86.7 percent yield) of a pale yellow crystalline product having a melting point of 42-43C.

EXAMPLE 9 Preparation of methyl 2,3,3-triiodoallyl ether 5.9 g of 2,3,3-triiodoallyl p-toluenesulfonate (m.p. l l4-l 16C, prepared by addition reaction of 3-iodo-2- propinyl p-toluenesulfonate with iodine or by reaction of p-toluenesulfonyl .chloride and 2,3,3-triiodoallyl alcohol in the presence of an alkali) was dissolved in layer was removed. The chloroform layer was washed with water, and by evaporating off the solvent at reduced pressure, about g of crude crystals were obtained. The crude crystals were recrystallized from methanol to afford 29.5 g (yield 79 percent) of almost colorless pillarto plate-like crystals having a melting point of 435 to 445C.

Elemental analysis values C H OL, (450) Calculated: C 10.07 H 1.12 Found: C 9.62 H 1.31

NMR (CCl 3.32 (singlet, 3H, CH;--O-.) 8(PP 4.04 (singlet, 2H. -CH, 0

(Note: The 8 values of NMR are those obtained using tetramethyllilane as an internal reference.)

EXAMPLE 11 TABLE 3 Amount Added Weight (g/ton 2nd 4th 6th 8th 10th Increase of feed week week week week week Index" 1 1 20.4 357.4 682.4 1084.4 4 1329.7 109.9 5 125.9 362.1 706.2' 1099.3 1408.4 116.4 10 147.6 388.0 764.0 1150.7 1512.1 125.0 20 120.4 350.2 647.3 990.7 1303.1 109.7 124.3 359.4 671.3 1030.5 1382.2 114.3 100 128.2 I 349.8 663.1 946.7 1223.7 101.2 200 106.5 343.2 686.3 1039.6 1298.3 107.3 Not Added 116.4 -341.2 611.6 926.7 1209.7 100.0 Procaine Penicillin G. 20 g 127.3 374.6 664.2 1012.9 1324.0 109.5

Index on the basis of the non-added group (100.0).

ml of dimethylformamide, and 0.55 g of sodiummethoxide was added thereto while ice-cooling and stirring.

The mixture was then stirred for aperiod of 30 minutes 50 under ice-cooling and then for a period of 1 hour at 25C, and thereafter 60 ml of ice-water was. added thereto to precipitate a crystalline product. The thus obtained product was separated by filtration, and washed first with water and then with a small amount of cold methanol to give 4.1g (91 percent yield) of pale yellow crystals having a melting point of 4243C.

EXAMPLE 10 Preparation of 2,3,3-triiodo-allyl-methyl ether 16 Grams of 3-iodo-2-propinyl-methyl ether was dissolved in 80 ml. of chloroform, and 25.4 g of iodine powder was added. The mixture was heated under reflux for 3 hours at a bath temperature of 70C, and then allowed to stand overnight at room temperature. It was further heated at 70C, and shaken with the gradual addition of a 1N aqueous solution of sodium thiosulfate until the color of the iodine disappeared. The aqueous methyl ether did not cause a decrease in body weight is evidence that this particular compound is little absorbed by the digestive tract and does not have sideeffects.

EXAMPLE l2 2,3,3-triiodo-allyl-methyl ether was finely divided in a mortar, and then diluted l0-fold with lactose. A field clinical test was performed using this formulation to treat the scours of 41 pigs. The formulation was administered orally twice on the first day and once a day for the next 3 to 4 days. The results are shown in Table 4,

. 3,859,362 ll 12 In this table, the symbols+H.++.+ andhave .the following meanings:

Hi watery feces 1+ muddy feces soft feces normal feces TABLE 4(a) Single Dosage (mg of pure Severity Body powder/Kg of Conditions Age Weight of body 1st 2nd 3rd 4th 5th Evalu No Sex days) (kg weight day day day day day ution 1 21 5 60 Cured 2 21 5 do. -H- do. 3 2| 5 do. {-1-} do. 4 2o 7 43 H- do 5 26 7- do. H d0. 6 26 7 do. H do. 7 7 3 100 -1+ do. 8 7 3 do. rH do. 9 13 4 75 rr do. l l3 4 do. H- do. 11 12 2 150 Hi do. 12 l2 2 do. H; do. I3 27 8 I00 {4- do. [4' 28 8 do. +ido. 15 22 60 H+ do to 4 75 1++ do 17 10 3 100 1H do l8 l0 3 do. -H do. I9 10 4 75 do. 20 I5 3 100 do. 2] l5 3 do. do 22 9 2.5 120 ii do. 23 9 1.5 200 do. 24 9 1.5 do. -i+ do. 25 8 2 150 1+} do. 26 34 5.5 -H- .H- do. 27 55 10.1 1+1 ++1 do. 28 54 6.1 4] +H 1+} do. 29 56 13.1; 51 m {r do. 30 35 4.1 49 H do. 31 35 4.3 47 4+ do. 32 35 4.! 49 -H do. 33 34 6 42 m do. 34 2o 27 so ih do. 35 10 50 4+ vv+ do. 36 28 4 do. {-H H} H do. 37 28 5 do. do. 38 40 5.3 47 -1+ do. 39 38 6.5 46 H- do. 40 39 5.9 42 do. 41 38 6.7 44 -H- -H do.

TABLE v4(b) Comparative Experiment Effect of Kanamycin Sulfate against Scours of Swine (Control) Single I Dosage Severity Body (mg/kg of Conditions Age weight of body 1st 2nd 3rd 4th 5th No Sex (days) (Kg) weight day day day day day 1 17 2.0 150 it 2 l7 2.l 145 7H- 18 2.2 135 18 2.3 130 5 l8 2.3 130 6 1o 40 +1- 7 22 2.7 1+ 8 22 2.5 -i+ -H-' 9. 19 3.0 100 1'0 19 2.6 115 -H- ll '15 2.6 115 12 15 2.3 130 it it 13 15 2.4 -H- l4 15 3.0 100 l5 l6 3.0 100 do. to 19 2.1; 105 I7 23 4.6 65 4- {3 531%? 2 7 2o 24 3.5 as +k. Hi Hi it 11+ TABLE 4(b)-Continued Comparative Experiment 7 Effect of Kanamycin Sulfate against Scours of v Swine (Control) Single Dosage Severity Body (mg/kg" of Conditions Age weight of body 1st 2nd 3rd 4th 5th Evalu- No. Sex (days) (Kg) weight day day day day day ation 21 7 2.0 I I50 ll -l+ -ido. 22 9 3.0 I00 +l 23 5.0 so Cured 24 l5 5.0 60 "H" do. -25 12 4.0 75. do, 26 l2 4.0 75 -H- do.

I The resultsshown in Table 4 demonstrate the supe-' t I rior effect of 2,3,3-triiodo-allyl methyl ether against 20 c=c-cH,-o-R

the diarrhea of swine. I

with references to specific embodiments thereof, it will While the invention has been described in detail and consistin 'ofmeth l,'eth l,-nto l and iso to I be apparent to one skilled in the art that various groups y P W P W changes and modifications can be made therein with- 5 ether of claim 1 wherein is out departing from the Spirit and Scope q a. The ether of claim 1 wherein R is ethyl;

What we claim is: v 4. The ether of claim 1 wherein R is 'n-propyl 1. An alkyl-2,3,3-triiodoallyl ether of the formula 5. The ether of claim 1 wherein R is isopropyl;

wherein R an alkyl .group selected from the group" UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION PATENT NO. 3,859,362

DATED January '7, 1975 |NVENTOR(S) I Yasuharu Sekizawa; Shigeo Seki; Bun zo Nomiya; Takemi Koeda; Fumio Kai; Naotoshi Akai; Yasushi Yusa; Fusguaki Fuku asu.

It rs certrfred that error appears In the ab0ve-rdentrfred patent and that and Letters Pat nt are hereby corrected as shown below:

Column 1, line 37, change I C C CH O R"to --I-CsC-CH -O-R--.

Column 1, line 5'7, change HC C CH O R"to -HG =.c -ct-I -o -R-.

Column 2, line 13, change "HC C CH O R to -I-IC 5C CH O R.

n H Column 6, lme 44, change C H OI to C H OI Column 10, line 10, change C H OI to -C I-I OI Signed and Scaled this A ttes t:

RUTH C. MASON C. MARSH Arrestin Offi ALL DAMN nmmissjuner 0f Patents and Trademarks UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION D Patent No. 3, 59, 362 Dated January 7, 1975 InVent01-(S) Xasuharu Sekizawa et a1 It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In The Heading:

ifhe claimed Priority was omitted. Should read:

. ----December 28, 1971 Japan..............105753/71 --January '7, 1972 Japan..............4311/72 --December 18, 1972 Japan. 126273/72 g Signed and Sealedthis eleventh D Of November 1975 [SEAL] A Nest:

RUTH C. MASON C. MA-RSHALL DANN Arresting ()ffiver (mnmissimwr nj'larents and Tradwnurks F ORM PO-105O (10-69) USCOMM-DC 60376-P69 

1. AN ALKYL-2,3,3-TRIIODOALLYL ETHER OF THE FORMULA
 2. The ether of claim 1 wherein R is methyl.
 3. The ether of claim 1 wherein R is ethyl.
 4. The ether of claim 1 wherein R is n-propyl.
 5. The ether of claim 1 wherein R is isopropyl. 